Insect repellents

ABSTRACT

The use of specific perfume ingredients, e.g. tricyclodecenyl allyl ether, to repel insects. The perfume ingredients may be used in a composition comprising from 0.1 to 40 percent by weight of one or more of the perfume ingredients. Preferably at least one of the perfume ingredients has a hydrophobicity such that the common logarithm of the octanol-water partition coefficient, log P, of the perfume ingredient is in the range 1.0 to 6.0.

This application is the National Phase of International ApplicationPCT/GB99/03107 filed Sep. 17, 1999 which designated the U.S. and thatInternational Application was published under PCT Article 21(2) inEnglish.

FIELD OF INVENTION

The present invention relates to the use of certain perfume ingredientsas an insect repellent, to compositions containing the perfumeingredients and to a method of repelling insects.

BACKGROUND

Insects have long been known as a nuisance and, for some insect genera,as a health hazard. Mosquitoes, for instance, are a proven vector ofdiseases, and the genus Aedes in particular is associated with yellowfever, dengue, encephalitis and malaria (Encyclopaedia Britannica).Although the problems may be reduced at source with the use of DDT andother chemical sprays in the breeding areas, fears over the persistenceof chlorchemicals combined with increasing mosquito resistance tocontrol chemicals (e.g. insecticides) have led to a reappraisal of themagnitude of the nuisance and the hazard. Physical barriers to theinsects are not always possible, e.g. in the open air, where some formof personal repellent is necessary.

It is also a feature of recent times that the more environmentally-awarepublic tend to question the safety of many chemicals which were formerlytaken for granted. One of these is the well-known personal insectrepellent N,N-diethyl-m-toluamide (abbreviated as DEET, and commerciallyavailable as Delphone™). This was originally seen as the naturalsuccessor to the parent molecule, N,N-diethylbenzamide which was foundto be strongly insect repellent but also irritating to human skin(McCabe et al., (1954), J. Org Chem. 19, 493-498). Fears over possibleallergenicity, disclosed in European Patent Application EP-A-0 167 266(Angus Chemical Company), as well as aversion to some of the physicalproperties of this compound such as oiliness and odour, have led to thesearch for less hazardous and more aesthetically acceptable methods ofrepelling insect pests, particularly mosquitoes.

REVIEW OF THE PRIOR ART

Certain compounds have long been known to possess insect deterrentproperties, some of this information coming from what might be termed“folk knowledge”. These materials include widely-known substances suchas Citronella, Tolu and Peru Balsams, Eucalyptus oils, Huon Pine andother similar oils [M. Bouvier, International Frag. Co-ord. 29 October1976]. Other materials known for their deterrent properties includethose having camphoraceous odours, such as Camphor itself, Cypress oils,Galbanum etc. [H&R Contact, 36, 1984].

Perfume ingredients with insect repellent properties used either alone,or in a perfume composition, and/or in some form of carrier or baseovercome many of the problems highlighted above. Many common types ofhousehold insects such as American cockroaches (periplaneta americana)are classified as pests and significant effort has been made to controlor eradicate them. A variety of chemicals that are effective inrepelling cockroaches has been discovered. These chemicals are used inthe household by applying or spraying them to surfaces of walls, floors,cabinets, containers, rugs, upholstery and carpeting, and in potentialnesting places for insects, such as inside walls and between floors.They have been used together with hardsurface cleaners (EP-A-0 619 363)and wax floor polishes (U.S. Pat. No. 3,018,217).

It is known in the art that organic materials and essential oils can berepellent against insects. In the art this has been measured in avariety of ways with different insects. The majority of the prior arthas been directed towards mosquitoes and in particular the species aedesaegyptii. The results of these studies has led to a list of preferredmaterials. Surprisingly we have found that additional perfumeingredients, preferably when used above certain limits in perfumecompositions can lead to enhanced insect repellency.

PCT Application WO 96/08147 discloses the use of a number of differentcompounds as insect repellents and also a method by which the repellencyof compounds to insects can be reliably tested.

SUMMARY OF THE INVENTION

It has now been surprisingly found that a number of perfume ingredientsare effective insect repellents.

Accordingly, the present invention provides the use of at least oneperfume ingredient selected from the group consisting of

Citral diethyl acetal (Citrathal*),

Tricyclodecenyl allyl ether (also known as 8-(allyloxy)tricyco[5.2.1.0.^(2.6) ]dec-3-ene) [Fleuroxene*],

2-(2-methylpropyl )-4-hydroxy4-methyltetrahydropyran [Florosa*],

N-methyl-N-phenyl-2-methylbutanamide [Gardamide*],

4-isobutyrate-3-methoxybenzaldehyde [Isobutavan*],

1 -hydroxy-2-methoxy4-propenylbenzene [Isoeugenol*],

2,2,7,7-tetramethyltricyclo[6.2.1.0^(1.6)]undecan-5-one[Isolongifolanone*],

7-formyl-5-isopropyl-2-methylbicyclo[2.2.2]oct-2-ene [Maceal*],

3-methyl-5-phenyl-1-pentanal [Mefranal*],

alpha iso methyl ionone (also known as 4-(2,6,6-trimethyl-2-cyclohexen-1-yl)-3-methyl-3-buten-2-one),

myrcenyl acetate (also known as 2-methyl-6-methylene-7-octen-2-ylacetate) [Neobergamate*],

10-isopropyl-2,7-dimethyloxaspiro [4.5] 3,6-decadiene [Neocaspirene*],

tricyclo[5.2.1.0^(2.6)]dec4-en-8-yl 2,2-dimethylpropanoate(Pivacyclene*),

2-phenylethyl pivalate (also known asphenylethyl-2,2-dimethylpropanoate) [Pivarose*]

and 2,4-dimethyl-4-phenyltetrahydrofuran [Rhubafuran*]

as an insect repellent. (*trade marks)

In another aspect, the invention provides a method of repelling insectsfrom an object or an airspace, comprising application to the object orinto the airspace, of an effective amount of at least one perfumeingredient selected from the group consisting of the aforementionedperfume ingredients. Typically, the object is a human body or a solidsurface such as a wall or floor.

The perfume ingredients from the aforementioned list which are moreeffective as insect repellents are those which have an octanol-waterpartition coefficient such that “log P” has a value in the range from1.0 to 6.0, more preferably 2.0 to 5.0, and particularly 2.5 to 4.5.“log P” is the common logarithm of the octanol-water partitioncoefficient and is well known in the literature as an indicator ofhydrophobicity and water solubility (see Hansch and Leo, ChemicalReviews, 526 to 616 (1971), 71 and Hansch, Quinlan and Lawrence J.Organic Chemistry, 347 to 350 (1968), 33). Where such values are notavailable in the literature they may be measured directly orapproximately estimated using mathematical algorithms. Softwareproviding such estimates is available commercially, for example ‘LogP’from Advanced Chemistry Design Inc.

In addition, those perfume ingredients which are more effective asinsect repellents have a “Kovats” index value in the range from 1150 to1650, more preferably 1250 to 1600, and particularly 1300 to 1560.Kovats indices are calculated from the retention time in a gaschromatographic measurement referenced to the retention time for alkanes(see Kovats, Helv. Chim. Acta 41, 1915 (1958)). Indices based on the useof a non-polar stationary phase have been used in the perfumery industryfor some years as a descriptor relating to the molecular size andboiling point of ingredients. A review of Kovats indices in the perfumeindustry is given by T Shibamoto in “Capillary Gas Chromatography inEssential Oil Analysis”, P Sandra and C Bicchi (editors), Huethig(1987), pages 259 to 274. A common non-polar phase which is suitable is100% dimethyl polysiloxane, as supplied, for example, under a variety oftrade names such as HP-1 (Hewlett Packard), CP Sil 5 CB (Chrompak), OV-1(Ohio Valley) and Rtx-1 (Restek).

A further property of the aforementioned perfume ingredients whichconfers good performance as an insect repellent is a capability offorming hydrogen bonds of greater than 60 on the Koppel Pal'm scale (J.Chem. Soc. Perkin Trans. 2, 1976, pp 1628).

The insect repellent perfume ingredients described herein are preferablyused in a composition, more preferably in a perfume composition,preferably at a concentration of at least 10%, more preferably at least30%, and particularly at least 50% by weight. The composition used inthe invention comprises at least one, and, more preferably, 3 or 4 ofthe perfume ingredients described herein. The individual perfumeingredients are preferably present at a concentration in the range from0.1% to 40%, more preferably, 0.5% to 20% by weight. The perfumecomposition may contain other known insect repellents, preferably ofpreviously known insect repellent perfume ingredients, preferably at aconcentration of at least 10%, more preferably at least 30%, andparticularly at least 50% by weight.

Compositions containing more than one of the aforementioned insectrepellent perfume ingredients preferably contain at least one suchperfume ingredient having a “log P” value in the range 1.0 to 6.0 or atleast one such perfume ingredient having a Kovats index in the range1150 to 1650, as hereinbefore defined, or at least one such perfumeingredient capable of forming hydrogen bonds of greater than 60 on theKoppel Pal'm scale.

Preferably, the perfume ingredients described herein are used to repelinsects, such as mosquitoes, particularly members of the genus Aedes andcockroaches.

Compositions used in accordance with the invention preferablyconstitute, or comprise, personal products or cosmetics for use on theskin and/or hair. Examples of such products include fine fragrances,colognes, skin creams, skin lotions, deodorants, talcs, bath oils,soaps, shampoos, hair conditioners and styling agents.

Alternatively, compositions used in accordance with the invention mayconstitute, or be comprised in, household products such as: airfresheners (including “heated” air fresheners in which insect repellentsubstances are released upon heating, e.g. electrically, or by burning[e.g. joss-sticks, candles]); hard surface cleaners; or laundry products(e.g. laundry detergent-containing compositions, conditioners).

Preferably the cosmetics, personal products and household productsdefined above comprise between 0.1% and 20%, more preferably 0.2% to 10%by weight of a composition used in accordance with the invention.

The compositions used in the invention may comprise additional materialsto produce desired products such as pleasing perfumes with usefulrepellent activity. Other materials which may be present in thecompositions (at concentrations from 0 to 99.95% w/w) includefragrances, solvents, diluents and fixatives known in the art, such as:

Aldehyde C11 (Undecylenic Aldehyde); Aldehyde iso C11 (GIV); Allspiceoil; Allyl cyclohexyl propionate; Amyl salicylate; Amylcinnamicaldehyde; Anethole; Anisic alcohol; Anisic aldehyde; Applinal (Q); Bayoil; Benzyl acetate; Benzyl benzoate; Benzyl cinnamate; Benzylpropionate; Benzyl salicylate; Bourgeonal (Q); Brahmanol; Camphor powdersynthetic; Cedarwood Virginian; Cedrenol; Cedryl acetate; Celestolide(IFF); Cineole; Cinnamic alcohol; cinnamic aldehyde; Cinnamon Leaf Oil:Cinnamyl acetate; cis-3-Hexenol; Citral; Citronella oil; Citronellal;Citronellol; Citronellyl acetate; Citronellyl oxyacetaldehyde; Cloveoil; Coriander oil; Coumarin; Cuminic aldehyde; Cyclamen aldehyde;Decanal; 9-Decenol; Dibenzyl ether; Dibutyl phthalate; DiethylPhthalate; Dihydromyrcenol; Dimethyl anthranilate; Dimethyl phthalate;Dimycretol (IFF); diphenylmethane; Diphenyl oxide; Dimethyl benzylcarbinyl acetate; Dodecanol; Dodecanal; Elemi oil; Ethyl methyl phenylglycidate; Ethyl cinnamate; Ethyl safranate (Q); ethyl vanillin;Eugenol; Evergreen oils (Pine oils etc.); gamma-Nonalactone;gamma-undecalactone; Geraniol; Geranium bourbon; Geranyl acetate;Geranyl formate; Gum Benzoin; Heliotropin; Hercolyn D (HER); Hexylbenzoate; Hexylcinnamic aldehyde; Hydratropic aldehyde dimethyl acetal;Hydroxycitronellal; Hydroxycitronellal dimethyl acetal; Indole; isoBomyl acetate; Isopropyl myristate; Iso-cyclocitral (GIV, IFF);Jasmacyclene; Jasmin oil; Lavandin Abrialis; Lavender oil; Lilial (GIV);Linalol; Linalyl acetate; Menthol Laevo; Methyl anthranilate; Methylcedryl ketone; Methyl dihydrojasmonate; Methyl ionone; Methyl myristate;Methyl naphthyl ketone; Methyl salicylate; Moss treemoss; Musk ketone;Nerol; Nerolin Bromelia; Neryl acetate; Nonanal; Oakmoss absolute;Octanol Olibanum resionoid; para-Cresyl phenylacetate;para-Methoxyacet6phenone; Patchouli oil; Peppermint oil; Petitgrain oil;2-Phenoxyethanol; Phenoxyethyl iso butyrate; Phenylethylacetate;Phenyethyl alcohol; Phenylethyl butyrate; Phenylethyl phenylacetate;Pimento oil; Pinene, alpha; Para-tert. butyl-cyclohexyl acetate;Resinoid Benzoin Siam; Rose oil; Rosemary oil; Sandalwood oil;terpineol; Tetrahydrolinalol; Tetrahydromuguol (IFF); Thyme Red;Undecanal; Vanillin; Verbena oil; Vetyvert Bourbon; Yara and Ylangylang.

Compounds are obtainable from the suppliers as indicated below: forthose compounds labelled “(Q)”,—Quest International,“(IFF)”—International Flavours & Fragrances, Inc., “(GIV)”—Givaudan,“(HER)”—Hercules B.V.

Other active and non-active materials may be present, such as:

acidic mucopolysaccharides and their salts, Aesculus hipocastanum, aloebarbadenisis Mil (Aloe Vera Linne), α-hydroxycarboxylic acids,α-ketocarboxylic acids, amide derivatives, amino acids, amphiphiliccyclodextrin derivatives, β-sitosterol, carboxy vinyl polymer watersoluble salts, carboxymethyl cellulose, carrageenan, chitin, chitosan,cholesterol, cholesterol fatty acid ester, collagen, dicarboxylic acidmonostearyl esters, di-fatty acid glycerol esters, digalactosyldiglyceride, ersterol, ethanol, extract of Swertia japonica Makino,fatty acids, fatty acid citrate esters, fatty alcohols, ginseng extract,glucose esters of higher fatty acids, guar gum, gum arabic,Hamamelidaceae (Hamamelis Virginiana Witch hazel), hyaluronic acid,hydrochyloesterol, hydroxybenzoic acids, isomaltose, isopropyl alcohol,lactose, lanosterol, lipids extracted from the biomass ofmicroorganisms, yeasts, moulds and bacteria, liposomes, locust bean gum,low molecular acidic mucopolysaccharides and their salts, low molecularweight humectant components, maltose, mineral oils, mineral powders,mono cis alkenoic acid, mucopolysaccharides, mycosterol, N-acyl lysines,N-isostearyl lysine, N-lauroyl lysine, N-myristyl lysine, N-palmitoyllysine, N-stearoyl lysine, natrium type bentonite, natural or syntheticaminoacid with protein or peptide bonds, NMF ingredients, nonvolatilesilicones, oil agents, oil matter, oligosaccharides, organic acids,pantothenic acid and its derivatives, petroleum jelly, phosphatidylethanolamine, phosphatidylcholine, phospholipids, polysaccharides,polyvinyl alcohol, polypeptides, proteins, raffinose, saponins, sodiumhyaluronate, sources of linoleic acid, sterols, sterol esters,stigmasterol, sucrose, sugar esters of higher fatty acids, sulphatide,sunscreens, surfactants, talc, thymosterol, tocopherol, mono-, di- ortri-glycerides, vitamins and analogues, vitamin E and/or its estercompounds, volatile silicone fluids, water-soluble moisture-retainingagents, water-soluble polymers and waxes.

The perfume ingredients used in the present invention can be used as thesole insect repellent in a composition or may be used in combinationwith other compounds which are effective insect repellents, includingpreviously known insect repellent perfume ingredients.

Thus, a further aspect of the invention comprises a mixture the perfumeingredients described herein with a known insect repellent. Known insectrepellents which are suitable for use in a mixture with at least oneperfume ingredient used in the present invention includeN,N-diethyl-m-toluamide (DEET); N,N-diethylbenzamide; citronella; Tolubalsam; Peru balsam; Eucalyptus oil; Huon pine oil; camphor; cypressoil; galbanum; diethyl phthalate; dimethyl phthalate; dibutyl phthalate;1,2,3a,4,5a,6,7,8,9,9a,9b-dodecahydro-3a,6,6,9a-tetramethyinaphtho[2,1-b] furan; 4-(tricyclo[5.2.1.0^(2.6)]decylidene-8)butanal;1-ethoxy-1-(2′-phenylethoxy)ethane; acetyl cedrene an propylidenephthalide.

A further composition according to the invention comprises a mixture ofat least one of the aforementioned perfume ingredients and a furthercompound, said further compound being present in an amount which issufficient to ensure that said further compound contributes to saidcomposition an insect repellent effect equivalent to a repellency of atleast 10% as determined by the insect repellency test defined inExample 1. Preferably, the further compound is present in saidcomposition in an amount which is sufficient to ensure that said furthercompound contributes an insect repellent effect equivalent to arepellency of at least 20% as determined by said insect repellency test.More preferably, the insect repellent effect contributed by the furthercompound is equivalent to a repellency of at least 30%.

The invention is illustrated by the following non-limiting examples andby reference to FIG. 1, which is a schematic representation of anapparatus suitable for testing compounds as insect repellents.

EXAMPLE 1 Insect Repellency Test—Mosquitoes

The effectiveness of the perfume ingredients as an insect repellent wastested using an apparatus similar to that disclosed in PCT ApplicationWO 96/08147 and illustrated in FIG. 1. The method is described fortesting of citral diethyl acetal but can be adapted to test any othercompound in place of citral diethyl acetal.

Four test chambers were prepared using 300 mm 200 gauge layflat tubing.The synthetic plastics tubing was attached to oblong stainless steelframes (150 mm by 150 mm by 900 mm) using double-sided adhesive tape.200 mm squares of cotton netting were used to cover the ends of thechambers and were secured using adhesive tape.

Mosquitoes (naive insects of the species Aedes aegypti, 4 to 7 days old)were introduced into each chamber 8 and the chambers 8 were kept in aseparate room until the test was ready to begin.

The exhaust fan which vents the room in which the test was performed wasswitched on.

Four targets 5 (only two shown) were prepared as follows: double layersof semi-porous membrane were stretched over the open ends of four openended glassware bulbs (diameter of open end 43 mm) and secured usingelastic bands. Testing was carried out at 27° C. The membranes were keptmoist and warmed above the ambient temperature throughout the test bypassing a supply of water (at 34° C.) through the glassware bulbs, so asto contact the inner surface of the membranes.

Citral diethyl acetal (30 microliters) was applied to a membrane andspread as evenly as possible across the membrane surface. This wasrepeated with two other membranes and the fourth membrane was leftuntreated as a control.

The chambers 8 containing the mosquitoes were positioned so that eachchamber had one netting end pressed against one of the targets 5. Glasspartitions in the form of a cross 6 were used to separate each target 5and chamber end from its neighbour.

600 mm 200 gauge layflat tubing was used to connect the various elementsas shown in FIG. 1. Air was forced by an inlet fan (not shown) over thefilters 2, 3, over the targets 5, and through the test chamberscontaining the mosquitoes. The separation of the membranes ensured thatair passing over a particular membrane would pass through only one testchamber 8.

The filters 2, 3 were used to remove volatile elements from the airpassing over the mosquitoes; filter 2 contained activated charcoal andfilter 3 contained a molecular sieve (Union Carbide type 5A zeolite).The material in each filter 2, 3 was held within the cells of a 25 mmthick sheet of aluminium honeycomb sandwiched between two sheets ofstainless steel mesh held in an aluminium frame. The filters 2, 3 werebolted by their frames to the inside of an aluminium tunnel such thatair passing along the tunnel passed through the filters 2, 3.

Four cameras 9 (only two shown) positioned downwind of the test chambers8 were each focused onto a particular target 5, and the images producedby the cameras displayed on a single monitor 15 by means of a quadsplitter 13. An electronic timer was used to project the date and timeonto the screen, and the video recorder 14 was used to record the data.

The mosquitoes in the test chambers 8 were activated by introduction ofa human breath stimulus upwind of the targets 5 and the number ofinsects attempting to bite each target 5 over the next ten minute periodwas recorded. After ten minutes, the recording was stopped and the testchambers 8 removed from their position immediately downwind of thetargets 5.

The targets 5 were left untouched (although still warmed and moistened)for one hour with the fans switched on, after which time the testchambers 8 were re-introduced and the test repeated to determine therepellency of the citral diethyl acetal one hour after application.

The numbers of mosquitoes attempting to bite each of the targets 5 wasnoted every 10 seconds throughout each ten minute recording period. The60 readings were used to produce a figure for the mean number of insectsbiting each target 5 during the ten minute test periods. The readingobtained for the untreated target 5 was used to give a measure of thebasic avidity of the mosquitoes used in the test and this was taken intoaccount when analysing the results.

EXAMPLE 2 Insect Repellency Test—Cockroaches

A set of ten containers was prepared, each approximately 300 mm×150mm×100 mm. Each contained two refuges made from small plastic plant potsapproximately 40 mm×40 mm×40 mm with a doorway approximately 20 mm×15mm. The inside of one refuge was treated with gpc base (formulationbelow) containing the test material. The second refuge was treated withunperfumed gpc base. A small quantity of food and water was placed ineach container. A single cockroach (periplaneta americana) was placedinto each of the ten containers and the normal daily light/dark cyclefollowed for 24 hours. The cockroaches were of mixed age and gender. Atthe end of the cycle, when the lights were on, the positions of thecockroaches were noted.

0 or 1 cockroaches in the test refuges was classified as good repellent,

2 cockroaches in the test refuges was classified as moderate repellent,and

3 or more cockroaches in the test refuges was classified as notrepellent.

If 2 or fewer cockroaches were in the test refuge and more than 2 wereoutside either refuge the test was repeated.

Gpc formulation Weight % Dobanol 91-5 5.0 Polyacrylic acid 0.2 Butyldigol 3.0 Sodium cumene sulphonate 1.0 Perfume ingredient 1.0 Water 89.8

What is claimed is:
 1. A method of repelling an insect selected from thegroup consisting of mosquitoes and cockroaches comprising subjectingsaid insect to an insect repelling amount of a composition comprising atleast three perfume ingredients selected from the group consisting oftricyclodecenyl allyl ether,2-(2-methylpropyl)-4-hydroxy-4-methyltetrahydropyran,N-methyl-N-phenyl-2-methylbutanamide,4-isobutyrate-3-methoxybenzaldehyde, 2,2,7,7-tetramethyltricyclo[6.2.1.0^(1.6)]undecan-5-one,7-formyl-5-isopropyl-2-methylbicyclo[2.2.2]oct-2-ene,3-methyl-5-phenylpentanal, alpha iso methyl ionone,10-isopropyl-2,7-dimethyloxaspiro [4.5]3,6-decadiene,tricyclo[5.2.1.0^(2.6)]dec-4-en-8-yl 2,2-dimethylpropanoate, phenylethylpivalate and 2,4-dimethyl-4-phenyltetrahydrofuran.
 2. The method ofclaim 1 wherein the composition compriss from 0.1 percent to 40 percentby weight of said perfume ingredients.
 3. The method of claim 2 whereinat least one of the perfume ingredients in the composition has ahydrophobicity such that the common logarithm of the octanol-waterpartition coefficient, log P, of the perfume ingredient is in the range1.0 to 6.0.
 4. The method of claim 2 or 3 wherein at least one of theperfume ingredients in the composition has a Kovats index in the range1150 to
 1650. 5. The method of claim 2 or 3 wherein at least one of theperfume ingredients in the composition has a capability of forminghydrogen bonds of greater than 60 on the Koppel Pal'm scale.
 6. Themethod of claim 2 wherein said composition comprises a personal product,a cosmetic or a household product.
 7. The method of claim 6 wherein saidcomposition comprises a fine fragrance, a cologne, a skin cream, a skinlotion, a deodorant, a talc, a bath oil, a soap, a shampoo, a hairconditioner, a styling agent, an air freshener, a hard surface cleaneror a laundry product.
 8. The method of claim 6 or 7 wherein saidpersonal product, cosmetic or household product contains between 0.1 percent and 20 per cent by weight of the composition.
 9. The method ofclaim 1 wherein the composition comprises 3 or 4 of said perfumeingredients.